Esters of flacourtiacea alcohols



Patented Mar. 26,1940.

ESTERS I Ozren Steifanovi and Georg Stefanovi, Zia mung; Yugoslavia N6 Drawing. Application February 20,1 937 Se- 'Thisinvention relates to lip oid-soluble s'ub-, stances-havingbactericidal properties.

It is known that the following substances have "af'killin g action towards acid-resisting bacteria:

oils from varieties ofFlacourtiacea' (Hydnocarpus, Astcriostzgma, macrocarpa, carpotroche brasilz'ehsis Endl'l, Oncobd echz'nata Oliver, Taralc- I togenos KurziiKinm as'. well'as the acids and alcohols obtained from these oils; further high 1o molecular ,alicyclic-aliphatic acids, such as high molecular cyclopropylg cyclopentyl-, cyclohexylfatty acids, and in fact all these acids as such or as their esters, salts, or addition products.

I The said substances have been investigated in havebeen' found to be insufiiciently active and have forthe most part been given up, partly also on account of undesired subsidiary actions.', According to the present invention the Flatconsist of courtiacea alcohols which essentially the compounds of the formula: I

wherein n stands for the numbers 10 an'd'l2 are employed in the form of their acid esters'or ester salts with polybasi'c inorganic acids;

particularly in vivo show especial bactericidal properties, and in fact not only against acidresisting bact'erianbut also against other varieties of pathogenic bacteria. In therapeutic doses they have no auxiliary efiect in' vivo and consequently they havea'high therapeutic index. 40

esters of the Flacourtiacea alcohols with polybasic inorganic acids proceeds according to generally known methods. The Flacourtiacea" alcohols themselves are obtainable in the following manner:

The oils of the Flacourtiacea (Asteriostigma 'macrocarpa, C'arpotroche brasiliensz's EndL, Hydnocarpus, Oncoba echinata Oliver, Taraktogcnos 'Kureii King) are reduced individually or in admixture, but in such a way thatdouble bonds present remain unchanged, orare only partly reduced. It is obvious that this reduction can be carried out not only with the oils themselves, but that the same may-first be 'saponifled and a cla s; '(o fjiato 4=sv j H H i m Fine a'cidsobt'ainedinthis way which substantially vitro, in vivo, and on the bed of sickness inthe case of infections by acid-resisting bacteria, but

It has unexpectedly been foundfthat" these acid esters as well as the ester'salts both vitro and The. preparation of these bactericidal acid rial No. 126,938.- In Yugoslavia February 2'7;

ija'ndryantcarpus' agid'of the mass; f

converted into other esters, e, 1 g." ethyl esters,

whereupon they are then reduced individually or in admixture to the corresponding alcohols.

The Flacourtiacea alcohols obtained .in this wayare converted in the known'man'ner into the acid esters; or ester salts of polybasic inorganic acids, suchas phosphoric and sulfuric acid.

I The substances prepared in this way may be used in the, form of the ester salts as healing agents for bacterial infections, particularlywith acid-resisting bacteria.

E ample.1001 rams of Flacourtiacea joil are heatedin ,500 grams absolute ethanolwuntil the oil is completely dissolved. 50 gramsofsodium are then a'ddedin small pieces to thissolution in the courseof about ten minutes.

About a "quarter of an hour after the addition of the sodiurmthe mixture is heated up to the boiling 1 of the ethanol and" further heatedluntil all r the sodium has completely disappeared, whichftakes about;oneh'our. After addition of, 200 cc. of

.water the ethanol is distilled off as far as possible in vacuum; and the remaining mixture, when v.11; has cooled down, is mixed with about 750 cc. 'of water, acidified and extracted with 500 cc.

ether, The ether is separated off and washedfirst with water, then with 3% potassium car-' bonate, andfinallywith water again upto the point of neutral reaction. l v

- I: The 1 ethereal solution is dried by .means of sodium sulphate, the ether distilled ofi and the mixture ofalcoholsiobtained is distilled in high ,vacuum. Boiling point (at 0.1 mm. pressure) -170. Yield 97%.

The alcohols obtained in this way are; converted into phosphoric acid esters according .to the following method: I

10 parts of theal'cohol obtained by reduction are dissolved in e0 parts of absolute etherandfi I The .whole mixture is heated for 24 hours up to the boiling of the ether, The whole is then cooled down to 0 and decantation is effected from parts of phosphorus pentoin'de are added thereto.

The ethereal solution is vaporised in vacuum, the esters of phosphoric acids are taken up with watenand for purification purposes precipitated yet again with common salt or alcohol. The

. yield corresponds to that calculated, The phosphoric acid esters obtained thus melt at 103-10 8, are readily soluble in waterwith swelling, readily soluble in ether, benzene, olive oil, and insoluble in alcohol. The esters obtained thus are used in aqueous solution in the form of neutral reacting salts.

The sulphuric acid ester is obtained according to the following process? grams of the said alcohols are dissolved 1 litre of absolute ether,..this solution .is then added drop-wise to a solution 0150 grams of chlorsulphonic acid in 1 litre of ether with stirring and cooling, and the whole allowed to stand for twelve hours. About 100 cc. ofwater are then added, theether is evaporated off in vacuum, 500 grams of water are then added again and this solution is saturated with common salt, whereupon the sulphuric acid esters precipitate out. In order to purify the same the esters'are repeatedly dissolved in water and saltedout. The

sulphuric acid esters obtained in this way are I I p I p 2,195,345 the phosphoric acids which have separated. out.

nance of their double bond, with phosphoric acid,

which esters are lipoid-soluble substances having bactericidal properties and formneutral watersoluble salts. I l

2. The acid esters of Flacourtiacea alcohols with a polyb'asic: inorganic acid of the group consisting of phosphoric and sulfuric acid, which esters are lipoid-soluble substances having bacble salts. I

3. The acid esters of Flacourtiaceaalcohols, obtained by carboxylic reduction of the "acids present in Flacourtiacea oils but with maintenance of their double bond, with sulfuric acid, which esters are lipoid-soluble substances havin bactericidal properties and form neutral watersoluble salts.

v OZREN STEFANOVIC. GEORG STEFANOVIC.

,tericidal properties and form neutral water-solu- 

